ABSTRACT
INTRODUCTION: Microchimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN. METHODS: Twenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences. RESULTS: MFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%). CONCLUSIONS: Our data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.
Subject(s)
Chimerism/statistics & numerical data , Genetic Predisposition to Disease/epidemiology , Kidney/pathology , Lupus Nephritis/genetics , Pregnancy Outcome , Biopsy, Needle , Case-Control Studies , Creatinine/blood , Female , Fetus/pathology , Humans , Immunohistochemistry , Linear Models , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/pathology , Lupus Nephritis/pathology , Male , Multivariate Analysis , Pregnancy , Prevalence , Risk Assessment , Sex Factors , Statistics, NonparametricABSTRACT
Experiments with novobiocin (NB) post-treatment were performed to verify its effect on the frequencies of micronuclei (MN) and chromosomal aberrations (CA) induced by g-irradiation (0.75, 1.5 and 3.0 Gy) in human lymphocytes at G0-phase. The frequencies of MN significantly decreased by 44 and 50 per cent, for the treatment with NB 50 µg/ml (30-min pulse) after radiation doses of 1.5 and 3.0 Gy, respectively. However, CA frequencies were not significantly affected. No significant effect on CA was observed when lymphocyte cultures were exposed to a single dose of 2.0 Gy at the G0-phase and posttreated with 25 µg/ml NB for three hours either immediately after irradiation (G0-phase) or after 24 h (S-phase). The significant suppressive effect of NB on MN frequencies supports the hypothesis that NB interaction with chromatin increases access to DNA repair enzymes.
